To look into theoretical basis of the molecular mechanism of deterioration, we took cassava(Manihot esculenta) stem, cassava stems of South China 8 (SC8) and Nanzhi 199 (NZ199) varieties at four aging degrees as materials and characterized the differentially expressed proteins(DEPs) in the stems responding to four aging degrees. The results showed that: 1) Compared to the non-aged stems, 38 DEPs of the stems of SC8 with two-day age were up-regulated by 11 and down-regulated by 27, 64 DEPs from the stems of SC8 with four-day age were up-regulated by 18 and down-regulated by 46, and 68 DEPs from the stems of SC8 at six-day age were up-regulated by 25 and down-regulated by 43. 2) Compared to the non-aged stems, 55 DEPs of the NZ199 at two-day age were up-regulated by 17 and down-regulated by 38, 63 DEPs from of NZ199 at four-day age were up-regulated by 23 and down-regulated by 40, and 84 DEPs of NZ199 at six-day age were up-regulated by 43 and down-regulated by 41. 3) Compared to the non-aged stems, two days aged and four days aged treatment, 17 of 19 common DEPs were identified from the age of six days for SC8 stems, while 30 of 36 common DEPs were identified from the age of six days for NZ199 stems. These 30 proteins were grouped into five functional categories, chaperone proteins, carbon metabolism and energy metabolism related proteins, transfer proteins, defense proteins, detoxification and antioxidant related proteins. 4) D-3-phosphoglycerate dehydrogenase, phosphoglycerate kinase, chitotriosidase-1-like, malic enzyme, probable cinnamyl alcohol dehydrogenase, 1-deoxy-D-xylulose-5-phosphate reductoisomerase were down-regulated, while probable glutathione S-transferase parC, isoflavone reductase-like, pathogenesis-related protein Bet v I family, heat shock protein, chaperonin CPN60, alpha amylase, ATP synthase subunit beta and enolase were up-regulated. 5) DEPs mainly participated in biological process, including response to oxidative stress, toxin catabolic process, glutathione metabolic process, protein folding and glycolytic process. The proteins were mainly located in mitochondria, chloroplasts, cytoplasm, cell wall, and etc, and played roles of binding, catalytic activity and oxidoreductase activity.